Intracranial hemorrhage combined with renal insufficiency, intensive blood pressure reduction may be fatal!

Introduction About 1/5 of patients with intracranial hemorrhage (ICH) have renal insufficiency or chronic kidney disease (CKD)
.

Although the commonly used treatment for acute intracranial hemorrhage is to quickly and drastically lower blood pressure, when patients have both types of diseases at the same time, treatment should be more cautious
.

The results of a post-hoc analysis of an open-label ATACH-2 trial involving nearly 1,000 ICH patients showed that patients with estimated glomerular filtration rate (eGFR) decreased after intensive antihypertensive treatment at a significantly higher risk of death and disability than patients with normal eGFR
.

 Research background The results of the INTERACT2 trial showed that in ICH patients, intensive blood pressure reduction has a slightly greater benefit than standard blood pressure reduction
.

In addition, the benefit was not significantly related to the patient's level of renal function
.

However, in the ATACH-2 trial, intensive blood pressure did not improve the ICH functional outcome, but increased the risk of adverse renal events
.

 In order to clarify the impact of renal function on the clinical outcome and treatment of ICH, the researchers performed post-mortem analysis on the data from the ATACH-2 trial
.

Study Design The ATACH-2 trial is an international, multi-center, open-label randomized controlled clinical trial
.

The initial cerebral hemorrhage volume of the patients participating in the trial was <60ml, and they were admitted within 4.
5 hours of onset, with systolic blood pressure >180mmHg, Glasgow Coma Scale (GCS score) <5, and international prothrombin time>1.
5
.

Patients were divided into intensive blood pressure control group and standard blood pressure control group: the target of intensive blood pressure control was 110-139mmHg, and the target of standard blood pressure control was 140-179mmHg
.

All patients received intravenous injection of nicardipine to keep their blood pressure within the target range of their respective groups and maintained for 24 hours
.

 The analysis excluded patients with renal failure (eGFR<15ml/min/1.
73㎡, regardless of whether they received renal replacement therapy), patients with acute kidney injury (AKI), patients before 1% of eGFR, and patients with disabilities or restricted daily activities before the onset
.

 According to the eGFR level at baseline, patients were divided into three subgroups: ≥90, 60-89 and <60ml/min/1.
73㎡
.

 The primary endpoint was the composite outcome of death or severe disability within 90 days, and the secondary endpoint was death within 90 days
.

 Research results A total of 974 ATACH-2 participants' data were included in the analysis
.

At baseline, the median eGFR was ml/min/1.
73㎡
.

There were 488 cases in the intensive blood pressure control group, of which the number of patients with eGFR≥90, 60-89 and <60ml/min/1.
73㎡ were 222, 184 and 82 respectively; there were 486 patients in the standard blood pressure control group, of which eGFR≥ The numbers of patients 90, 60-89 and <60ml/min/1.
73㎡ were 229, 179 and 78 respectively
.

01 Compared with ICH patients with normal renal function (eGFR≥90ml/min/1.
73㎡), the mortality and disability rate of patients with eGFR<60ml/min/1.
73㎡ are higher for the primary endpoint (aOR=2.
02, 95% CI, 1.
25 -3.
26), but patients with eGFR 60-89ml/min/1.
73㎡ compared with those with normal renal function, the mortality and disability rate were not statistically different (OR=1.
01, 95% CI, 0.
70-1.
46)
.

02 Compared with the standard blood pressure control group, the secondary endpoint of the intensive blood pressure control group is that the more patients whose eGFR decreases, the higher the mortality rate
.

The ORs of patients in the intensive blood pressure control group with eGFR≥90, 60-89, and <60ml/min/1.
73㎡ compared with those in the standard blood pressure control group were 0.
89 (95% CI, 0.
55-1.
44), 1.
13 (0.
68-1.
89) and 3.
60 (1.
47-8.
80), the P value is 0.
02
.

 Analysis shows that the reduction of eGFR is related to the adverse results after ICH, and the safety of patients with renal insufficiency should be paid attention to in intensive antihypertensive treatment
.

Discussion Patients with a history of stroke or stroke are often accompanied by chronic kidney disease (CKD).
Therefore, for the treatment of ICH and stroke, CKD is an important factor to be considered
.

 The author believes that because the brain and kidney are similarly susceptible to vascular damage, the small blood vessels in the brain are likely to have been damaged in people with reduced eGFR
.

Therefore, active blood pressure control may more easily limit cerebral perfusion, leading to delayed brain function recovery
.

 Professor Craig Anderson of the University of New South Wales in Australia pointed out that one in five ICH patients will have moderate to severe renal impairment
.

This kidney function damage may be caused by high blood pressure, which may lead to a worse prognosis for such patients with ICH
.

Anderson recommends that ICH patients with decreased eGFR be treated with caution, especially when choosing whether to enable intensive blood pressure control
.

These tests suggest that the time to lower the blood pressure to the target blood pressure should be 1 hour instead of 30 minutes
.

In addition, it may be a reasonable decision to avoid drastically reducing the systolic blood pressure from >220mmHg to <140mmHg
.

 To clarify the mechanism of the relationship between the reduction of eGFR and the increased risk of disability or death after intensive antihypertensive treatment requires further research
.

In addition, more research is needed to explore and confirm blood pressure intervention methods suitable for patients with ICH and renal insufficiency
.

 References: 1.
Fukuda-Doi M, Yamamoto H, Koga M, Doi Y, et al.
Impact of Renal Impairment on Intensive Blood-Pressure-Lowering Therapy and Outcomes in Intracerebral Hemorrhage: Results From ATACH-2.
Neurology.
2021 Jul 1:10.
1212/WNL.
0000000000012442.
2.
Erik Greb.
Intensive BP-Lowering for ICH Potentially Deadly in Chronic Kidney Disease.
Medscape.
July 15, 2021